Aminoacetonitriles have been prepared by reacting aldehydes with alkali metal cyanides followed by isolation of the cyanohydrin and subsequent reaction with ammonia in a suitable solvent. Isolation of the cyanohydrin can be difficult due to the solubility of cyanohydrin in aqueous medium. Moreover, isolation of the cyanohydrin is inconvenient and increases the risk of exposure to hydrogen cyanide.
Aminoacetonitriles have also been prepared without isolation of the cyanohydrin by the Strecker synthesis using an alkali metal cyanide and an ammonium salt under aqueous conditions. The Strecker synthesis, however, is not practical in cases where the aminoacetonitriles are subsequently used under nonaqueous conditions because it is difficult to isolate the aminoacetonitriles which are unstable and often water soluble.
In addition, aminoacetonitriles have been prepared by reacting aldehydes with trimethylsilyl cyanide in the presence of a catalytic amount of zinc iodide to obtain silyl blocked cyanohydrins which have been reacted with ammonia using protic solvents such as methanol to obtain aminoacetonitriles. Mai and Patil in an article entitled, "Facile Synthesis of alpha-Aminonitriles" which appeared in TETRAHEDRON LETTERS, Vol. 25, No. 41, pp. 4583-4586, 1984, disclose the preparation of aminonitriles by reacting trimethylsilyloxynitriles with various amines in methanol. On page 4583 of the article, Mai and Patil state that the amination step requires alcohol as a solvent. Moreover, they explicitly state that the amination did not proceed in an aprotic medium.
Mai and Patil in another article entitled, "A Fast N-Substituted alpha-Aminonitrile Synthesis" which appeared in SYNTHETIC COMMUNICATIONS, Vol. 15, No. 2, pp. 157-163, 1985, disclose the preparation of aminonitriles by reacting an aldehyde, an amine and trimethylsilyl cyanide at 100.degree. C. for one minute. On page 158 of the article, Mai and Patil explicitly state that the silyloxynitrile does not react with an amine in an aprotic solvent even at elevated temperatures. In contrast to the articles by Mai and Patil, the present invention uses a water miscible amide solvent which is an aprotic solvent.
Mai and Patil also state in their article entitled, "A Fast N-Substituted alpha-Aminonitrile Synthesis" that the reaction is not applicable to the preparation of primary aminonitriles since gaseous ammonia does not react with the carbonyl compounds in the presence of aprotic solvents. In contrast, the present inventor has determined that gaseous ammonia reacts with silyl blocked cyanohydrin compounds in the presence of a water miscible amide solvent. Amide solvents are relatively involatile, thus, allowing passage of ammonia to occur over several hours without incurring significant solvent loss. Futhermore, clean conversion to the aminoacetonitriles occurs when amide solvents are used. The use of amide solvents allows the aminoacetonitriles to be converted to important intermediates such as thiadiazoles and acylamino derivatives. Other solvents are not as useful in these respects. For example, use of pyridine or acetonitrile as solvents in the amination step leads to the formation of by-products.
The processes of the present invention for preparing aminoacetonitriles and thereafter thiadiazole derivatives are represented as follows. The numbers appearing under each compound will be referred to throughout this document. ##STR1##